المؤلفون: Nanda Kishore Routhu, Narayanaiah Cheedarla, Venkata Satish Bollimpelli, Sailaja Gangadhara, Venkata Viswanadh Edara, Lilin Lai, Anusmita Sahoo, Ayalnesh Shiferaw, Tiffany M. Styles, Katharine Floyd, Stephanie Fischinger, Caroline Atyeo, Sally A. Shin, Sanjeev Gumber, Shannon Kirejczyk, Kenneth H. Dinnon, Pei-Yong Shi, Vineet D. Menachery, Mark Tomai, Christopher B. Fox, Galit Alter, Thomas H. Vanderford, Lisa Gralinski, Mehul S. Suthar, Rama Rao Amara

المصدر: Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021)

مصطلحات موضوعية: Science

الوصف: Efficient vaccines for SARS-CoV-2 are needed. Here, the authors show that a trimeric form of the receptor-binding domain of SARS-CoV-2 spike adjuvanted with alum-3M-052 protects non-human primates from disease and inhibits infection.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/eb5e727593c442beadc6bb289092f047Test

المؤلفون: Nicholas K. Hurlburt, Emilie Seydoux, Yu-Hsin Wan, Venkata Viswanadh Edara, Andrew B. Stuart, Junli Feng, Mehul S. Suthar, Andrew T. McGuire, Leonidas Stamatatos, Marie Pancera

المصدر: Nature Communications, Vol 11, Iss 1, Pp 1-7 (2020)

مصطلحات موضوعية: Science

الوصف: Currently there is neither a vaccine nor an effective treatment strategy available for COVID19. Here, Hurlburt et al. provide the crystal structure of a patient-derived monoclonal antibody neutralizing SARS-CoV-2 via shedding of the S1 subunit and competing for the receptor binding domain.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/db69f59e4cb349f0a8827bbe7916aae3Test

المؤلفون: Madeleine F. Jennewein, Anna J. MacCamy, Nicholas R. Akins, Junli Feng, Leah J. Homad, Nicholas K. Hurlburt, Emilie Seydoux, Yu-Hsin Wan, Andrew B. Stuart, Venkata Viswanadh Edara, Katharine Floyd, Abigail Vanderheiden, John R. Mascola, Nicole Doria-Rose, Lingshu Wang, Eun Sung Yang, Helen Y. Chu, Jonathan L. Torres, Gabriel Ozorowski, Andrew B. Ward, Rachael E. Whaley, Kristen W. Cohen, Marie Pancera, M. Juliana McElrath, Janet A. Englund, Andrés Finzi, Mehul S. Suthar, Andrew T. McGuire, Leonidas Stamatatos

المصدر: Cell Reports, Vol 36, Iss 2, Pp 109353- (2021)

مصطلحات موضوعية: SARS-CoV-2, SARS-CoV-1, S2 subunit, RBD, NTD, neutralization, Biology (General), QH301-705.5

الوصف: Summary: SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency and antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralize the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2211124721007294Test; https://doaj.org/toc/2211-1247Test

الوصول الحر: https://doaj.org/article/f492dbc1e9954938a7e8625d4e1dc65eTest

المؤلفون: Stacey A Lapp, Venkata Viswanadh Edara, Austin Lu, Lilin Lai, Laila Hussaini, Ann Chahroudi, Larry J Anderson, Mehul S Suthar, Evan J Anderson, Christina A Rostad

المصدر: PLoS ONE, Vol 16, Iss 8, p e0256482 (2021)

مصطلحات موضوعية: Medicine, Science

الوصف: BackgroundThe effects of pre-existing endemic human coronavirus (HCoV) immunity on SARS-CoV-2 serologic and clinical responses are incompletely understood.ObjectivesWe sought to determine the effects of prior exposure to HCoV Betacoronavirus HKU1 spike protein on serologic responses to SARS-CoV-2 spike protein after intramuscular administration in mice. We also sought to understand the baseline seroprevalence of HKU1 spike antibodies in healthy children and to measure their correlation with SARS-CoV-2 binding and neutralizing antibodies in children hospitalized with acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome (MIS-C).MethodsGroups of 5 mice were injected intramuscularly with two doses of alum-adjuvanted HKU1 spike followed by SARS-CoV-2 spike; or the reciprocal regimen of SARS-Cov-2 spike followed by HKU1 spike. Sera collected 21 days following each injection was analyzed for IgG antibodies to HKU1 spike, SARS-CoV-2 spike, and SARS-CoV-2 neutralization. Sera from children hospitalized with acute COVID-19, MIS-C or healthy controls (n = 14 per group) were analyzed for these same antibodies.ResultsMice primed with SARS-CoV-2 spike and boosted with HKU1 spike developed high titers of SARS-CoV-2 binding and neutralizing antibodies; however, mice primed with HKU1 spike and boosted with SARS-CoV-2 spike were unable to mount neutralizing antibodies to SARS-CoV-2. HKU1 spike antibodies were detected in all children with acute COVID-19, MIS-C, and healthy controls. Although children with MIS-C had significantly higher HKU1 spike titers than healthy children (GMT 37239 vs. 7551, P = 0.012), these titers correlated positively with both SARS-CoV-2 binding (r = 0.7577, PConclusionsPrior murine exposure to HKU1 spike protein completely impeded the development of neutralizing antibodies to SARS-CoV-2, consistent with original antigenic sin. In contrast, the presence of HKU1 spike IgG antibodies in children with acute COVID-19 or MIS-C was not associated with diminished neutralizing antibody responses to SARS-CoV-2.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/41da9f03dae647768fd862268e480defTest

المؤلفون: Stacey A. Lapp (7405628), Venkata Viswanadh Edara (11349005), Austin Lu (8638089), Lilin Lai (9413285), Laila Hussaini (11349008), Ann Chahroudi (531553), Larry J. Anderson (8599890), Mehul S. Suthar (11349011), Evan J. Anderson (3369149), Christina A. Rostad (10820737)

مصطلحات موضوعية: Biochemistry, Medicine, Microbiology, Cell Biology, Neuroscience, Physiology, Biotechnology, Immunology, Cancer, Hematology, Infectious Diseases, Virology, original antigenic sin, multisystem inflammatory syndrome, gmt 37239 vs, 14 per group, hku1 spike protein, +groups%22">xlink "> groups, hku1 spike antibodies, 2 spike protein, 2 spike followed, mount neutralizing antibodies, children following sars, hku1 spike, %22">xlink ">, 2 spike, spike proteins, neutralizing antibodies, igg antibodies, 2 serologic

الوصف: (PDF)

العلاقة: https://figshare.com/articles/journal_contribution/The_ARRIVE_essential_10_Compliance_questionnaire_/16525913Test

الإتاحة: https://doi.org/10.1371/journal.pone.0256482.s002Test

المؤلفون: Rajesh M. Valanparambil, Jennifer Carlisle, Susanne L. Linderman, Akil Akthar, Ralph Linwood Millett, Lilin Lai, Andres Chang, Ashley A. McCook-Veal, Jeffrey Switchenko, Tahseen H. Nasti, Manpreet Saini, Andreas Wieland, Kelly E. Manning, Madison Ellis, Kathryn M. Moore, Stephanie L. Foster, Katharine Floyd, Meredith E. Davis-Gardner, Venkata-Viswanadh Edara, Mit Patel, Conor Steur, Ajay K. Nooka, Felicia Green, Margaret A. Johns, Fiona O'Brein, Uma Shanmugasundaram, Veronika I. Zarnitsyna, Hasan Ahmed, Lindsay E. Nyhoff, Grace Mantus, Michael Garett, Srilatha Edupuganti, Madhusmita Behra, Rustom Antia, Jens Wrammert, Mehul S. Suthar, Madhav V. Dhodapkar, Suresh Ramalingam, Rafi Ahmed

المصدر: Journal of Clinical Oncology. 40:3808-3816

مصطلحات موضوعية: Cancer Research, Oncology

الوصف: PURPOSE To examine COVID-19 mRNA vaccine–induced binding and neutralizing antibody responses in patients with non–small-cell lung cancer (NSCLC) to SARS-CoV-2 614D (wild type [WT]) strain and variants of concern after the primary 2-dose and booster vaccination. METHODS Eighty-two patients with NSCLC and 53 healthy volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2–specific binding and neutralizing antibody responses were evaluated by Meso Scale Discovery assay and live virus Focus Reduction Neutralization Assay, respectively. RESULTS A majority of patients with NSCLC generated binding and neutralizing antibody titers comparable with the healthy vaccinees after mRNA vaccination, but a subset of patients with NSCLC (25%) made poor responses, resulting in overall lower (six- to seven-fold) titers compared with the healthy cohort ( P = < .0001). Although patients age > 70 years had lower immunoglobulin G titers ( P = < .01), patients receiving programmed death-1 monotherapy, chemotherapy, or a combination of both did not have a significant impact on the antibody response. Neutralizing antibody titers to the B.1.617.2 (Delta), B.1.351 (Beta), and in particular, B.1.1.529 (Omicron) variants were significantly lower ( P = < .0001) compared with the 614D (WT) strain. Booster vaccination led to a significant increase ( P = .0001) in the binding and neutralizing antibody titers to the WT and Omicron variant. However, 2-4 months after the booster, we observed a five- to seven-fold decrease in neutralizing titers to WT and Omicron viruses. CONCLUSION A subset of patients with NSCLC responded poorly to the SARS-CoV-2 mRNA vaccination and had low neutralizing antibodies to the B.1.1.529 Omicron variant. Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::14d319511fd2013c1714abacd9af343cTest
https://doi.org/10.1200/jco.21.02986Test

المؤلفون: Prabhu S. Arunachalam, Madeleine K. D. Scott, Thomas Hagan, Chunfeng Li, Yupeng Feng, Florian Wimmers, Lilit Grigoryan, Meera Trisal, Venkata Viswanadh Edara, Lilin Lai, Sarah Esther Chang, Allan Feng, Shaurya Dhingra, Mihir Shah, Alexandra S. Lee, Sharon Chinthrajah, Sayantani B. Sindher, Vamsee Mallajosyula, Fei Gao, Natalia Sigal, Sangeeta Kowli, Sheena Gupta, Kathryn Pellegrini, Gregory Tharp, Sofia Maysel-Auslender, Sydney Hamilton, Hadj Aoued, Kevin Hrusovsky, Mark Roskey, Steven E. Bosinger, Holden T. Maecker, Scott D. Boyd, Mark M. Davis, Paul J. Utz, Mehul S. Suthar, Purvesh Khatri, Kari C. Nadeau, Bali Pulendran

المصدر: Nature.

مصطلحات موضوعية: Multidisciplinary

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::a0eae77aa5c2863eebf79c0f8033ec4cTest
https://doi.org/10.1038/s41586-023-05977-xTest

المؤلفون: Yang You, Kathleen Borgmann, Venkata Viswanadh Edara, Satomi Stacy, Anuja Ghorpade, Tsuneya Ikezu

المصدر: Journal of Extracellular Vesicles, Vol 9, Iss 1 (2020)

مصطلحات موضوعية: astrocytes, extracellular vesicles, extracellular matrix, exosome, il-1β, inflammatory diseases, neurodegenerative diseases, proteomics, Cytology, QH573-671

الوصف: Astrocytes in the central nervous system (CNS) provide supportive neural functions and mediate inflammatory responses from microglia. Increasing evidence supports their critical roles in regulating brain homoeostasis in response to pro-inflammatory factors such as cytokines and pathogen/damage-associated molecular pattern molecules in infectious and neurodegenerative diseases. However, the underlying mechanisms of the trans-cellular communication are still unclear. Extracellular vesicles (EVs) can transfer a large diversity of molecules such as lipids, nucleic acids and proteins for cellular communications. The purpose of this study is to characterize the EVs cargo proteins derived from human primary astrocytes (ADEVs) under both physiological and pathophysiological conditions. ADEVs were isolated from human primary astrocytes after vehicle (CTL) or interleukin-1β (IL-1β) pre-treatment. Label-free quantitative proteomic profiling revealed a notable up-regulation of proteins including actin-associated molecules, integrins and major histocompatibility complex in IL-1β-ADEVs compared to CTL-ADEVs, which were involved in cellular metabolism and organization, cellular communication and inflammatory response. When fluorescently labelled ADEVs were added into primary cultured mouse cortical neurons, we found a significantly increased neuronal uptake of IL-1β-ADEVs compared to CTL-ADEVs. We further confirmed it is likely due to the enrichment of surface proteins in IL-1β-ADEVs, as IL-1β-ADEVs uptake by neurons was partially suppressed by a specific integrin inhibitor. Additionally, treatment of neurons with IL-1β-ADEVs also reduced neurite outgrowth, branching and neuronal firing. These findings provide insight for the molecular mechanism of the ADEVs’ effects on neural uptake, neural differentiation and maturation, and its alteration in inflammatory conditions.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2001-3078Test

الوصول الحر: https://doaj.org/article/97b4c95002df44f58e46f92e0c055d4cTest

المؤلفون: Venkata Viswanadh Edara, Shruthi Nooka, Jessica Proulx, Satomi Stacy, Anuja Ghorpade, Kathleen Borgmann

المصدر: Biomedicines; Volume 8; Issue 11; Pages: 479

مصطلحات موضوعية: astroglia, HIV-associated neurocognitive disorders (HAND), IL-6 regulation, Wnt/β-catenin signaling, neuroinflammation, NF-κB crosstalk

الوصف: Reactive astrogliosis is prominent in most neurodegenerative disorders and is often associated with neuroinflammation. The molecular mechanisms regulating astrocyte-linked neuropathogenesis during injury, aging and human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) are not fully understood. In this study, we investigated the implications of the wingless type (Wnt)/β-catenin signaling pathway in regulating astrocyte function during gliosis. First, we identified that HIV-associated inflammatory cytokines, interleukin (IL)-1β and tumor necrosis factor (TNF)-α induced mediators of the Wnt/β-catenin pathway including β-catenin and lymphoid enhancer-binding factor (LEF)-1 expression in astrocytes. Next, we investigated the regulatory role of β-catenin on primary aspects of reactive astrogliosis, including proliferation, migration and proinflammatory responses, such as IL-6. Knockdown of β-catenin impaired astrocyte proliferation and migration as shown by reduced cyclin-D1 levels, bromodeoxyuridine incorporation and wound healing. HIV-associated cytokines, IL-1β alone and in combination with TNF-α, strongly induced the expression of proinflammatory cytokines including C-C motif chemokine ligand (CCL)2, C-X-C motif chemokine ligand (CXCL)8 and IL-6; however, only IL-6 levels were regulated by β-catenin as demonstrated by knockdown and pharmacological stabilization. In this context, IL-6 levels were negatively regulated by β-catenin. To better understand this relationship, we examined the crossroads between β-catenin and nuclear factor (NF)-κB pathways. While NF-κB expression was significantly increased by IL-1β and TNF-α, NF-κB levels were not affected by β-catenin knockdown. IL-1β treatment significantly increased glycogen synthase kinase (GSK)-3β phosphorylation, which inhibits β-catenin degradation. Further, pharmacological inhibition of GSK-3β increased nuclear translocation of both β-catenin and NF-κB p65 into the nucleus in the absence of any other inflammatory stimuli. HIV+ human ...

وصف الملف: application/pdf

العلاقة: Molecular and Translational Medicine; https://dx.doi.org/10.3390/biomedicines8110479Test

الإتاحة: https://doi.org/10.3390/biomedicines8110479Test

المؤلفون: Anamika Patel, Sanjeev Kumar, Lilin Lai, Chennareddy Chakravarthy, Rajesh Valanparambil, Elluri Seetharami Reddy, Kamalvishnu Gottimukkala, Prashant Bajpai, Dinesh Ravindra Raju, Venkata Viswanadh Edara, Meredith E. Davis-Gardner, Susanne Linderman, Kritika Dixit, Pragati Sharma, Grace Mantus, Narayanaiah Cheedarla, Hans P. Verkerke, Filipp Frank, Andrew S. Neish, John D. Roback, Carl W. Davis, Jens Wrammert, Rafi Ahmed, Mehul S. Suthar, Amit Sharma, Kaja Murali-Krishna, Anmol Chandele, Eric A. Ortlund

المصدر: bioRxiv : the preprint server for biology.

مصطلحات موضوعية: History, Polymers and Plastics, Structural Biology, Business and International Management, Molecular Biology, Industrial and Manufacturing Engineering

الوصف: A detailed understanding of the molecular features of the neutralizing epitopes developed by viral escape mutants is important for predicting and developing vaccines or therapeutic antibodies against continuously emerging SARS-CoV-2 variants. Here, we report three human monoclonal antibodies (mAbs) generated from COVID-19 recovered individuals during first wave of pandemic in India. These mAbs had publicly shared near germline gene usage and potently neutralized Alpha and Delta, but poorly neutralized Beta and completely failed to neutralize Omicron BA.1 SARS-CoV-2 variants. Structural analysis of these three mAbs in complex with trimeric spike protein showed that all three mAbs are involved in bivalent spike binding with two mAbs targeting class-1 and one targeting class-4 Receptor Binding Domain (RBD) epitope. Comparison of immunogenetic makeup, structure, and function of these three mAbs with our recently reported class-3 RBD binding mAb that potently neutralized all SARS-CoV-2 variants revealed precise antibody footprint, specific molecular interactions associated with the most potent multi-variant binding / neutralization efficacy. This knowledge has timely significance for understanding how a combination of certain mutations affect the binding or neutralization of an antibody and thus have implications for predicting structural features of emerging SARS-CoV-2 escape variants and to develop vaccines or therapeutic antibodies against these.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4e105e50e50003d113de3898609102acTest
https://pubmed.ncbi.nlm.nih.gov/36324804Test